PSMA expression in the neo-vasculature of solid tumors

Abstract

2181 Background:
 Prostate Specific Membrane Antigen (PSMA) is a type II transmembrane metallo-peptidase overexpressed in prostate cells. Initially thought to be highly specific for prostate and cancer, recent evidence suggest that PSMA is also expressed in endothelial cells associated with non-prostatic solid tumors. Thus far only a limited number of solid tumors have been investigated in detail for PSMA expression in the neovasculature. Because of its potential use as a vascular targeting molecule we determined the expression of PSMA in a representative collection of a variety of solid tumor entities including gastric, colo-rectal, renal-cell and urothelial carcinoma.
 Experimental design:
 PSMA expression was determined by immunohistochemistry in formalin-fixed paraffin-embedded tissue sections of 119 cases of primary gastric cancer, 130 cases of primary colorectal cancers, 19 cases of renal cell carcinoma (RCC), 18 cases of urothelial carcinoma of the bladder and 23 urothelial carcinoma of the renal pelvis. Immunoreactivity was scored semiquantitatively based on staining intensity and distribution. Expression data were correlated with clinicopathological information.
 Results: PSMA expression was detected in tumor-associated neo-vasculature of 79 of 119 (66.4%) of gastric and 110 of 130 (84.6%) of colorectal cancers. Interestingly, 15 (12%) colorectal cancer samples showed also a strong epithelial PSMA staining. There was a trend for high grade tumors to higher PSMA expression (Spearman r = 0.18, P = 0.046) and men generally had higher PSMA level than women (Spearman r = 0.23, P = 0.009) in colorectal cancers. 17 of 19 (89 %) samples of RCC showed strong staining for PSMA in tumor-associated endothelial cells. Non-clearcell carcinoma samples showed no PSMA expression. Thirty-six of fourty-two (88%) urothelial carcinomas exhibited detectable PSMA expression.
 Conclusions:
 We confirm previous reports on the tumor specific expression of PSMA in neo-vasculature in a large sample collection of solid malignancies. PSMA is frequently expressed in the tumorvasculature but expression levels vary significantly within one tumor entity and between different entities. Further studies investigating the biological significance and regulation of PSMA expression are therefore needed. Because of its highly tumor-specific expression and its unique biological characteristics PSMA represents an interesting target for anti-angiogenic therapies in solid tumors.